Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street, Toronto, ON, Canada M5T 2S8; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada.
Department of Psychiatry, Laval University, Québec City, QC, Canada; Laval University Robert-Giffard Research Centre, Québec City, QC, Canada; Clinique Marie-Fitzbach, Québec City, QC, Canada.
J Affect Disord. 2014 Mar;156:1-7. doi: 10.1016/j.jad.2013.10.043. Epub 2013 Nov 15.
Most adults with major depressive disorder (MDD) fail to achieve remission with index pharmacological treatment. Moreover, at least half will not achieve and sustain remission following multiple pharmacological approaches. Herein, we succinctly review treatment modalities proven effective in treatment-resistant depression (TRD).
We conducted a review of computerized databases (PubMed, Google Scholar) from 1980 to April 2013. Articles selected for review were based on author consensus, adequacy of sample size, the use of a standardized experimental procedure, validated assessment measures and overall manuscript quality.
The evidence base supporting augmentation of conventional antidepressants with atypical antipsychotics (i.e., aripiprazole, quetiapine, and olanzapine) is the most extensive and rigorous of all pharmacological approaches in TRD. Emerging evidence supports the use of some psychostimulants (i.e., lisdexamfetamine) as well as aerobic exercise. In addition, treatments informed by pathogenetic disease models provide preliminary evidence for the efficacy of immune-inflammatory based therapies and metabolic interventions. Manual based psychotherapies remain a treatment option, with the most compelling evidence for cognitive behavioral therapy. Disparate neurostimulation strategies are also available for individuals insufficiently responsive to pharmacotherapy and/or psychosocial interventions.
Compared to non-treatment-resistant depression, TRD has been less studied. Most clinical studies on TRD have focused on pharmacotherapy-resistant depression, with relatively fewer studies evaluating "next choice" treatments in individuals who do not initially respond to psychosocial and/or neurostimulatory treatments.
The pathoetiological heterogeneity of MDD/TRD invites the need for mechanistically dissimilar, and empirically validated, treatment approaches for TRD.
大多数患有重度抑郁症（MDD）的成年人未能通过指数药物治疗达到缓解。此外，至少有一半的人在多次药物治疗后无法达到并维持缓解。在此，我们简要回顾了在治疗抵抗性抑郁症（TRD）中被证明有效的治疗方法。
我们对 1980 年至 2013 年 4 月的计算机数据库（PubMed、Google Scholar）进行了回顾。选择进行综述的文章基于作者共识、样本量充足、使用标准化实验程序、验证评估措施和整体手稿质量。
支持用非典型抗精神病药物（即阿立哌唑、喹硫平和奥氮平）来增强传统抗抑郁药的证据基础是所有 TRD 药物治疗中最广泛和最严格的。新出现的证据支持使用一些精神兴奋剂（即 lisdexamfetamine）和有氧运动。此外，基于发病机制疾病模型的治疗方法为免疫炎症为基础的治疗方法和代谢干预提供了初步的证据。基于手册的心理疗法仍然是一种治疗选择，其中最有说服力的证据是认知行为疗法。对于对药物治疗和/或心理社会干预反应不足的个体，也有不同的神经刺激策略。
与非治疗抵抗性抑郁症相比，TRD 研究较少。大多数关于 TRD 的临床研究都集中在药物治疗抵抗性抑郁症上，相对较少的研究评估了对心理社会和/或神经刺激治疗无初始反应的个体的“下一个选择”治疗。
MDD/TRD 的病理生理异质性需要针对 TRD 采用机制不同且经过实证验证的治疗方法。
